855778-40-4

Usage

Uses

Used in Pharmaceutical Research:
(R)-methyl 2-(((benzyloxy)carbonyl)amino)-3-(7-methyl-1H-indazol-5-yl)propanoate is used as a potential drug candidate in the pharmaceutical industry for the treatment of certain diseases. Its unique structure, which includes a variety of functional groups, may contribute to its effectiveness in targeting specific biological pathways or receptors.
The specific properties and potential uses of (R)-methyl 2-(((benzyloxy)carbonyl)amino)-3-(7-methyl-1H-indazol-5-yl)propanoate would need to be further studied and evaluated to determine its suitability as a therapeutic agent. This may involve in vitro and in vivo testing, as well as assessments of its pharmacokinetics, pharmacodynamics, and safety profile. If successful, (R)-methyl 2-(((benzyloxy)carbonyl)amino)-3-(7-methyl-1H-indazol-5-yl)propanoate could become an important tool in the development of new treatments for a range of medical conditions.

Upstream product

• 855778-39-1 (R)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate 
• 87-62-7 2,6-dimethylaniline 
• 138385-59-8 4-iodo-2,6-dimethylbenzenamine hydrochloride 
• 1337918-86-1 (Z)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate 
• 1337918-87-2 (R)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate 
• 1676-81-9 N-benzyloxycarbonyl-L-serine methyl ester 
• 21149-17-7 methyl 2-(benzyloxycarbonylamino)acrylate 
• 1414976-13-8 methyl (R)-3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonylamino)-propanoate methanesulfonate 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 855778-41-5 (R)-2-(benzyloxycarbonylamino)-3-(7-methyl-1H-indazol-5-yl)propanoic acid 

Relevant academic research and scientific papers

INTRANASAL PHARMACEUTICAL COMPOSITIONS OF CGRP INHIBITORS

Provided is pharmaceutical composition for intranasal delivery, wherein the pharmaceutical composition includes a therapeutically active ingredient including a CGRP inhibitor. Also provided is a method for delivering a CGRP inhibitor to a subject, wherein

Selection of an enantioselective process for the preparation of a CGRP receptor inhibitor

(R)-N-(3-(7-Methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl) piperazine-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide (1) is a potent calcitonin gene-related peptide (CGRP) receptor antagonist. We have developed a convergent, stereoselective, and economical synthesis of the hydrochloride salt of 1 and demonstrated the synthesis on a multikilogram scale. Two different routes to the chiral indazolyl amino ester subunit were developed utilizing either a Rh-catalyzed asymmetric hydrogenation or a biocatalytic process to install the single chiral center. The advantages and disadvantages of each of these process routes are discussed, as are challenges addressed in the assembly of the final drug substance.

CGRP RECEPTOR ANTAGONIST

The disclosure generally relates to the compound of formula I, (R)-N-(3-(7-methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide, including pharmaceutically acceptable salts, which is a CGRP-receptor antagonist. The disclosure also relates to pharmaceutical compositions and methods for using the compound in the treatment of CGRP related disorders including migraine headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cancer.

Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7- methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl) piperidine-1-carboxamide (BMS-694153): A potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Early chemistry leads suffered from modest potency, significant CYP3A4 inhibition, and poor aqueous solubility. Herein, we describe the optimization of these leads to give 4 (BMS-694153), a molecule with outstanding potency, a favorable predictive toxicology profile, and remarkable aqueous solubility. Compound 4 has good intranasal bioavailablity in rabbits and shows dose-dependent activity in validated in vivo and ex vivo migraine models.

Novel processes for the preparation of CGRP-receptor antagonists and intermediates thereof

The invention relates to novel processes for the preparation of small molecule antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”) and intermediates thereof.

HETEROCYCLIC ANTI-MIGRAINE AGENTS

The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.